A factor has been derived from the serum of a patient with membranoproliferative glomerulonephritis (MPGN) which is capable of activating C3 through the alternative complement pathway. The factor is a nonimmunoglobulin protein which is cryoprecipitable at 4 degrees C. It has been isolated as a 20-24s protein. The molecular weight, estimated in several polyacrylamide gel systems is between 345 and 390,000. The protein isolated does not appear to be aggregated, insofar as these PAGE results occur in a system containing hypertonic urea. The factor is heat labile at 56 degrees C. Incubation for 30 minutes at 56 degrees C causes the gamma migrating protein to lose its biological activity and to be converted to an alpha migrating protein. The gamma-migrating C3 activating factor is present in the cryoprecipitate from the index case with beta-1-H-globulin. The beta-1-H globulin in the cryoprecipitable fraction of the sera has an altered electrophoretic mobility when it is in the presence of C3AF. Therefore it is possible that C3AF is responsible for alternative complement pathway activation through interaction with beta-1-H and deregulation of the pathway. The majority of patients with Type I (subendothelial deposit) membranoproliferative glomerulonephritis have been shown to have C3AF and beta-1-H, as well as C3 in glomerular deposits. We propose further studies on the nature and distribution of C3AF. C3AF will be isolated and its possible interaction with isolated beta-1-H studied. Further studies will be carried out in order to determine the presence of C3AF and its quantity in other patients with MPGN and in other renal diseases. We will attempt to isolate C3AF in quantities large enough to test for biological activity in vivo in experimental animal models.